The University of Miami's South Florida Center for Reducing Health Disparities (SUCCESS) aims to improve the health of South Florida's most vulnerable populations through collaborative, participatory research. Our primary focus has been to improve early detection and prevention of diseases that disproportionately affect communities, disenfranchised from the formal healthcare system. Towards this end, we have tested the effectiveness of multiple Community Health Worker (CHW)-led interventions to improve screening uptake for four priority health conditions: HIV, Hepatitis C, Colorectal Cancer (CRC), and cervical cancer. However, a major limitation of all such projects is that each has existed as distinct, standalone initiative targeting a specific community and/or individuals who meet narrow eligibility criteria. The current proposal will address this gap. We propose to develop and implement a clinical trial that offers screening for all four health conditions in a no-clinical setting, circumventing known structural and access barriers to care. Our partners in this application are our longstanding collaborators: the Health Choice Network- a consortium of Federally Qualified Health Centers (FQHCs), and the Center for Haitian Studies. Based on their input, we propose a pragmatic trial of 900 people ages 50-65 who self-identify as Hispanic, Haitian, and/or African and have not been appropriately screened for the aforementioned diseases of interest. Our specific aim is to determine whether a CHW led intervention, which provides innovative, home based screening increases uptake among medically underserved individuals who are in need of at least of these tests. This multi-modality approach will use oral swabs for HIV, finger stick testing for Hepatitis C, Fecal Immunochemical Testing (FIT) for CRC, and self- sampling for Human Papilloma Virus, the primary cause of cervical cancer. The proposed pragmatic trial, grounded in the tenets of community-based participatory research (CBPR), will help identify optimal strategies for delivering prevention services to medically-vulnerable population sub-groups. Our study testing innovative, cost sensitive approaches will help inform health reform strategies that increasingly prioritize population health and precision medicine.